02/CE/B124 and 07/CE/B1368). “
“The H2-dependent methylene-tetrahydromethanopterin dehydrogenase (Hmd), also known as the [Fe]-hydrogenase, is found only in methanogens without cytochromes. In contrast to the binuclear metal centers of the [NiFe]- and [FeFe]-hydrogenases, the [Fe]-hydrogenase

contains Midostaurin datasheet only a single Fe atom, which is coordinated by a novel guanylylpyridinol cofactor in the active site. The biosynthesis of the cofactor is not well understood and the responsible genes are unknown. However, seven genes (hmd co-occurring genes, hcg) encoding proteins of unknown function are always associated with the hmd gene. In the model methanogen Methanococcus maripaludis, we used a genetic background in which a deletion of hmd had a distinct growth phenotype, and made null-mutations in each hcg gene as well as in a gene encoding the Hmd paralog HmdII, which is hypothesized to function

as a scaffold for cofactor synthesis. Deletions in all seven hcg genes resulted in the same growth phenotype as a deletion in hmd, suggesting they are required for Hmd function. In all cases, genetic complementation of the mutation restored the wild-type phenotype. A deletion in hmdII had no effect. “
“The Per–ARNT–Sim (PAS) domain serine/threonine kinase PAS kinase is involved in energy selleck chemicals flux and protein synthesis. In yeast, PSK1 and PSK2 are two partially redundant PASK homologs. We recently generated PSK2 deletion mutant and showed that Psk2 acts as a nutrient-sensing why protein kinase to modulate Ultradian clock-coupled respiratory oscillation in yeast. Here, we show that deletion of PSK1 increased the sensitivity of yeast cells to oxidative stress (H2O2 treatment) and partially inhibited cell growth; however, the growth

of the PSK2-deleted mutant was similar to that of the wild type. Superoxide dismutase-1 (SOD1) mRNA and protein levels were lower in PSK1-deletion mutant than the wild type. The mRNA levels of stress response genes CTT1, HSP104, ATH1, NTH1 and SOD2 were similar in both the PSK1-deleted mutant and wild-type yeast. Furthermore, intracellular accumulation of reactive oxygen species (ROS) was noted in PSK1-deleted mutant. These results suggest that PSK1 induces SOD1 expression to protect against oxidative stress in yeast. “
“Geotrichum candidum ATCC 204307 was previously found to generate phenyllactic acid (PLA) and indoleacetic acid (ILA) in complex culture media. In this study, a relationship between concentrations of PLA, ILA, and hydroxy PLA (OH-PLA) and initial concentrations of phenylalanine, tryptophan, and tyrosine, added respectively as unique sources of nitrogen in synthetic medium, was established.

, 2009). In their analyses, a collection of 3300 Xac transposon-insertion mutants was screened for their ability to produce disease in planta, and among the ORFs disrupted, XAC0798 (amy) was found to be the one that resulted in some alteration in bacterial virulence. In contrast, in our experiments, the disruption of XAC0798 by the insertion of pPM2a (Fig. 2) did not produce any alteration in pathogenesis or virulence even using the same host plant, Rangpur lime, used by Laia et al. (2009). This discrepancy could be explained tentatively by the selection of a hypothetical Xac amy∷transposon

mutant strain harboring an additional mutation (perhaps spontaneous) on a region essential for pathogenesis in the screenings performed by Laia et al. (2009). Xac has a repertoire of >1600 hypothetical ORFs, and

probably a considerable part of these might be involved in pathogenesis and virulence to its host selleck products plants. Therefore, the GFP expression vectors described here constitute not only extra tools for the study of specific proteins but also an auxiliary method for protein functional assignments, similar to what has already been done with B. subtilis and Caulobacter crescentus (Meile et al., 2006; Werner et al., 2009). P.M.M.M. was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP_2006/59494-9). We thank M.A. Machado (IAC-Cordeirópolis) for allowing us to use their microscope facilities. We thank F.J. Gueiros-Filho for Carfilzomib concentration the gift of pEA18 and the anti-GFP antibody. We thank L.F.F. Donin (Olympus Brazil) for technical support. This work was funded by FAPESP grant 2004/09173-6. Table S1. Oligonucleotides. Fig. S1. Growth curves of Xac wild type, and the mutant strains Xac amy:pPM2a and Xac amy:pPM2a-XAC3408. Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material)

should be directed to the corresponding author for the article. “
“The genes lukS-PV and lukF-PV for Panton–Valentine leukocidin (PVL) that confers high virulence to Staphylococcus aureus are located on the prophages (PVL phages) which have been classified into group 1 and 2 sfi21-like Siphoviridae. We report novel PVL phages lysogenized in Tolmetin ST59 methicillin-resistant Staphylococcus aureus (MRSA) strains isolated in Japan (JCSC7247) and Taiwan (JCSC5967). The genomes of φ7247PVL and φ5967PVL showed more than 99% identity, and the regions containing the five genes located at both ends of the prophages, int (integrase), hol (holin), ami (amidase), lukS-PV, and lukF-PV, are highly homologous to extant PVL phages. The genes for the structural module are less homologous to these phages, but are highly homologous to non-PVL phages belonging to group 3 Sfi21-like Siphoviridae, for example φN315.

3 deaths per 1000 person-years of follow up [95% confidence interval (CI) 11.0–13.8]. The median age was 43 years [standard JQ1 deviation (SD) 9.8 years] in AHOD and 38 years (SD 9.6 years) in TAHOD. The majority of patients were male; 94% of patients were male in AHOD compared with 71% of patients in TAHOD. The main exposure category in AHOD was homosexual contact (78%) compared with heterosexual contact (68%) in TAHOD. Low incidences of HAD were observed: 36 (2%) and five deaths in AHOD and 14 (<1%) and one death in TAHOD. Similarly, low incidences of PML were observed; two (<1%) and no deaths in AHOD and 10 (<1%) and two deaths in TAHOD (Table 1). The median observed CPE based on treatment

time was 8 [interquartile range (IQR) 7–9]. Prior neurocART had been received by 1267 AHOD patients (53%) compared with 2454 TAHOD patients (70%). The average prior cumulative neurocART http://www.selleckchem.com/HIF.html duration in AHOD was 13 months (SD 20.7 months) compared with 10 months (SD 15.4 months) in TAHOD. Of the patients in AHOD, 1129 (47%) had neurocART as the first cART whereas in TAHOD, 2630 (75%) had neurocART as the first cART. There was no significant difference in the risk of mortality between neurocART and non-neurocART groups for either the univariate or the multivariate models (Table 2). The unadjusted

hazard ratio (HR) associated with neurocART use was 0.87 (95% CI 0.68–1.12). Variables associated with survival in univariate models were age at entry, HIV exposure category, HBV coinfection, HCV coinfection, ADI, CD4 cell count, HIV viral load, prior DNA ligase treatment, regimen count and duration of prior cART (not neurocART) exposure. Covariates retained in the final multivariate model were age, HIV exposure category, HBV coinfection, ADI, CD4 cell count and regimen. In this model the adjusted HR

associated with neurocART use was 0.89 (95% CI 0.69, 1.14) (Table 2). Covariates associated with increased mortality in this model were age >50 years compared with age <30 years (HR 2.47; 95% CI 1.53–3.99), exposure from IDU compared with MSM (HR 2.01; 95% CI 1.33–3.05), lower CD4 cell count and regimen fourth or more compared with first (HR 1.57; 95% CI 1.13–2.17). Analyses by cohort showed no significant difference in the risk of mortality between neurocART and non-neurocART groups; the adjusted HR associated with neurocART use was 0.81 (95% CI 0.59–1.12) for AHOD and 0.92 (95% CI 0.59–1.43) for TAHOD. All other sensitivity analyses showed similar, nonsignificant differences in risk of mortality for the neurocART and non-neurocART groups (Table 3). There was no significant difference in the risk of AIDS or death between the neurocART and non-neurocART groups for either of the univariate or multivariate models (Table 4). The adjusted HR associated with neurocART use was 0.93 (95% CI 0.71–1.23).

, 2005). Clinical chemistry analyses were conducted on Lenvatinib nmr serum (ADVIA 1650, Bayer Healthcare Diagnostics). The following parameters were measured: alkaline phosphatase, aspartate transaminase (AST), alanine transaminase (ALT), creatine kinase, blood urea nitrogen, creatinine, bilirubin, albumin, total protein, serum iron, calcium, magnesium and glucose. CRP was analysed using a dendrimer-coupled cytidine diphosphocholine sandwich enzyme-linked immunosorbent assay

(ELISA) (Heegaard et al., 2009). Detection antibodies were from DAKO (Glostrup, Denmark) and pooled pig serum calibrated against a human CRP calibrator (DAKO A0073) was used as the standard. The detection limit was 67 ng mL−1 (human equivalents) and all samples were run in duplicate. IL-6 and IL-1β serum concentrations were determined by sandwich ELISAs from R&D Systems (Duoset DY686 and Duoset DY681, respectively; Gamma-secretase inhibitor Abingdon, UK). Samples were run in duplicate in a dilution of 1 : 2 with a detection limit of 125 pg mL−1 (IL-6) and 62.5 pg mL−1 (IL-1β), using R&D Systems calibrators as the standard. Tumour necrosis factor (TNF)-α serum concentrations were determined using a sandwich ELISA from R&D Systems (Quantikine PTA00). Samples were run in duplicate in a dilution of 1 : 2 with a detection limit of 46.8 pg mL−1, using R&D Systems calibrators as a standard. At inoculation,

most of the S. aureus-infected animals showed dyspnoea, which started about 1 min after the inoculation and lasted about 2 min. Two animals had apnoea and had to be ventilated mechanically by means of repeated pressure on

the thorax for about 2 min. The dyspnoea and apnoea were sometimes accompanied by repeated clonic seizures, each lasting approximately 5 s. After the respiration had become stable, diffuse erythema of the skin appeared in several of the pigs, but disappeared after Ribonucleotide reductase 10–15 min. Recovery from sedation was uneventful in all cases, and the animals were able to stand less than 1 h PI. Seven to eight hours PI, signs of clinical disease were observed in all the infected animals. They became lethargic and remained in lateral or sternal recumbency most of the time and stood up reluctantly on manipulation. The respiration was forced and the body temperature was elevated and remained high throughout the experiment. At 12 h PI, an acute abscess surrounded by a haemorrhagic rim was found in the lung of one S. aureus-infected animal (I-1). At 24 h, two of the infected animals (II-1 and II-3) had multiple haemorrhagic processes in the lungs. The third pig (II-2) had pulmonary oedema and hyperaemia as well as a single pulmonary abscess surrounded by a haemorrhagic rim. At 48 h, all infected animals had pulmonary processes, either in the form of petechiae or small abscesses.

, 2005). Clinical chemistry analyses were conducted on NVP-BGJ398 order serum (ADVIA 1650, Bayer Healthcare Diagnostics). The following parameters were measured: alkaline phosphatase, aspartate transaminase (AST), alanine transaminase (ALT), creatine kinase, blood urea nitrogen, creatinine, bilirubin, albumin, total protein, serum iron, calcium, magnesium and glucose. CRP was analysed using a dendrimer-coupled cytidine diphosphocholine sandwich enzyme-linked immunosorbent assay

(ELISA) (Heegaard et al., 2009). Detection antibodies were from DAKO (Glostrup, Denmark) and pooled pig serum calibrated against a human CRP calibrator (DAKO A0073) was used as the standard. The detection limit was 67 ng mL−1 (human equivalents) and all samples were run in duplicate. IL-6 and IL-1β serum concentrations were determined by sandwich ELISAs from R&D Systems (Duoset DY686 and Duoset DY681, respectively; mTOR inhibitor Abingdon, UK). Samples were run in duplicate in a dilution of 1 : 2 with a detection limit of 125 pg mL−1 (IL-6) and 62.5 pg mL−1 (IL-1β), using R&D Systems calibrators as the standard. Tumour necrosis factor (TNF)-α serum concentrations were determined using a sandwich ELISA from R&D Systems (Quantikine PTA00). Samples were run in duplicate in a dilution of 1 : 2 with a detection limit of 46.8 pg mL−1, using R&D Systems calibrators as a standard. At inoculation,

most of the S. aureus-infected animals showed dyspnoea, which started about 1 min after the inoculation and lasted about 2 min. Two animals had apnoea and had to be ventilated mechanically by means of repeated pressure on

the thorax for about 2 min. The dyspnoea and apnoea were sometimes accompanied by repeated clonic seizures, each lasting approximately 5 s. After the respiration had become stable, diffuse erythema of the skin appeared in several of the pigs, but disappeared after Guanylate cyclase 2C 10–15 min. Recovery from sedation was uneventful in all cases, and the animals were able to stand less than 1 h PI. Seven to eight hours PI, signs of clinical disease were observed in all the infected animals. They became lethargic and remained in lateral or sternal recumbency most of the time and stood up reluctantly on manipulation. The respiration was forced and the body temperature was elevated and remained high throughout the experiment. At 12 h PI, an acute abscess surrounded by a haemorrhagic rim was found in the lung of one S. aureus-infected animal (I-1). At 24 h, two of the infected animals (II-1 and II-3) had multiple haemorrhagic processes in the lungs. The third pig (II-2) had pulmonary oedema and hyperaemia as well as a single pulmonary abscess surrounded by a haemorrhagic rim. At 48 h, all infected animals had pulmonary processes, either in the form of petechiae or small abscesses.

, 2002). PCR products were electrophoresed in a 1% agarose gel and purified with the kit GenElute PCR Clean-up (Sigma) following the manufacturer’s instructions. The purified products were cloned in pGEM-T

Easy Vector System II kit (Promega) or directly used for sequencing. Sequencing was accomplished using the kit BigDye Terminator v3.1 Cycle Sequencing (Applied Biosystems) and an ABI Prism 3130 DNA Sequencer (Applied Biosystems). The sequences were analyzed using chromaslite v2.01 and seqmanii (DNASTAR) programs and subjected to blast searches to retrieve the most closely related sequences. The presence of tRNA genes was determined using tRNAscan-SE 1.21 software (Lowe & Eddy, 1997). Previously reported 16S rRNA gene and ISR sequences from T. soleae and related species, retrieved from GenBank database (http://www.ncbi.nlm.nih.gov/genbank/) and those obtained in this study, were aligned by using the program clustalw (http://www.ebi.ac.uk/Tools/msa/clustalw2/) GSI-IX nmr and examined for areas of similarity and variability between different species and strains. On the basis of the alignments, two variable regions were chosen and a pair of primers was designed by using the primer3 program GSK3235025 order (http://frodo.wi.mit.edu/; Rozen & Skaletsky, 2000). Primers were synthesized by Thermo Scientific (Ulm, Germany). The PCR amplifications were carried out using the commercial

kit RedTaq ReadyMix (Sigma), which included all necessary reagents except the primers and DNA template. The PCR mixture consisted of reaction buffer (10 mmol L−1 Tris–HCl pH 8.3, 50 mmol L−1 KCl, 1.5 mmol L−1 MgCl2), 200 μmol L−1 GNE-0877 of each dNTP, 200 nmol L−1 of each primer,

3 U of Taq DNA polymerase, template DNA, and double-distilled water up to a final volume of 50 μL. The amplification was performed in a Mastercycler gradient (Eppendorf) as follows: an initial denaturation at 94 °C for 5 min followed by 45 amplification cycles (denaturation at 94 °C for 1 min, annealing at 57 °C for 45 s, and extension at 72 °C for 1 min), and a final elongation at 72 °C for 5 min. DNA from strain T. soleae a47 was included as a positive control and distilled water as a negative control. PCR products were electrophoresed on a 1% agarose TBE gel stained with SYBR Safe DNA Gel Stain (Invitrogen); a 1-kb DNA ladder (Biotools) was included as a molecular weight marker. To test the specificity of the primers in the PCR procedure, nine T. soleae strains, isolated from three different hosts and including the type strain, and 81 strains of other species, most of them taxonomically and/or ecologically related, were used as positive and negative controls, respectively (Table 1). For PCR amplification, 100 ng DNA template was used for each strain. The detection limit was evaluated using 10-fold serially diluted DNA, isolated from strain T. soleae a47, over the range 100 ng to 100 fg. Large amounts of DNA (0.5–3 μg) were also assayed.

, 2002). PCR products were electrophoresed in a 1% agarose gel and purified with the kit GenElute PCR Clean-up (Sigma) following the manufacturer’s instructions. The purified products were cloned in pGEM-T

Easy Vector System II kit (Promega) or directly used for sequencing. Sequencing was accomplished using the kit BigDye Terminator v3.1 Cycle Sequencing (Applied Biosystems) and an ABI Prism 3130 DNA Sequencer (Applied Biosystems). The sequences were analyzed using chromaslite v2.01 and seqmanii (DNASTAR) programs and subjected to blast searches to retrieve the most closely related sequences. The presence of tRNA genes was determined using tRNAscan-SE 1.21 software (Lowe & Eddy, 1997). Previously reported 16S rRNA gene and ISR sequences from T. soleae and related species, retrieved from GenBank database (http://www.ncbi.nlm.nih.gov/genbank/) and those obtained in this study, were aligned by using the program clustalw (http://www.ebi.ac.uk/Tools/msa/clustalw2/) Smoothened antagonist and examined for areas of similarity and variability between different species and strains. On the basis of the alignments, two variable regions were chosen and a pair of primers was designed by using the primer3 program PF-02341066 research buy (http://frodo.wi.mit.edu/; Rozen & Skaletsky, 2000). Primers were synthesized by Thermo Scientific (Ulm, Germany). The PCR amplifications were carried out using the commercial

kit RedTaq ReadyMix (Sigma), which included all necessary reagents except the primers and DNA template. The PCR mixture consisted of reaction buffer (10 mmol L−1 Tris–HCl pH 8.3, 50 mmol L−1 KCl, 1.5 mmol L−1 MgCl2), 200 μmol L−1 Dipeptidyl peptidase of each dNTP, 200 nmol L−1 of each primer,

3 U of Taq DNA polymerase, template DNA, and double-distilled water up to a final volume of 50 μL. The amplification was performed in a Mastercycler gradient (Eppendorf) as follows: an initial denaturation at 94 °C for 5 min followed by 45 amplification cycles (denaturation at 94 °C for 1 min, annealing at 57 °C for 45 s, and extension at 72 °C for 1 min), and a final elongation at 72 °C for 5 min. DNA from strain T. soleae a47 was included as a positive control and distilled water as a negative control. PCR products were electrophoresed on a 1% agarose TBE gel stained with SYBR Safe DNA Gel Stain (Invitrogen); a 1-kb DNA ladder (Biotools) was included as a molecular weight marker. To test the specificity of the primers in the PCR procedure, nine T. soleae strains, isolated from three different hosts and including the type strain, and 81 strains of other species, most of them taxonomically and/or ecologically related, were used as positive and negative controls, respectively (Table 1). For PCR amplification, 100 ng DNA template was used for each strain. The detection limit was evaluated using 10-fold serially diluted DNA, isolated from strain T. soleae a47, over the range 100 ng to 100 fg. Large amounts of DNA (0.5–3 μg) were also assayed.

coli’ pathway-based proteolytic system in E. coli was performed using homologous recombination technology. Using the strain constructed in ‘Replacement of the tnaA gene with the trpR gene’, the DNA fragment consisting of Ptrp, click here the kan gene, and ORF of the ubi4 gene was inserted in-frame upstream of the target gene (dnaB, fab, or pyrG) originally present in the chromosome

by homologous recombination (Product No. 33, 34, 60 in Table S2 and Fig. 1a). For the construction of the GlmU, DnaX, DnaG, IspA, Era, PyrH, or Der, we used a construction strategy that can be applied in cases where direct recombination of the essential target gene (the method described in ‘Construction of the bacterial strain targeting DnaB,FabB, or PyrG’) is unsuccessful or if the target gene has an operon structure. Using the strain constructed in ‘Replacement of the tnaA gene with the trpR gene’, the DNA fragment of ORF of the ubi4 gene fused

in-frame to ORF of the target gene (glmU, dnaX, dnaG, der, pyrH, era, or ispA) was inserted downstream of the tryptophan promoter present in the chromosome by homologous recombination, and then each original gene in the chromosome was deleted by homologous recombination with DNA fragment encoding the kan gene (Fig. 1b). Colony formation Selleck Y27632 assay was performed using the strains

constructed in ‘Construction of tryptophan promoter-dependent expression system in E. coli’ (Table 2). No colony was detected in the LB agar plate containing Trp (1 mg mL−1) alone or containing Trp (1 mg mL−1) plus IPTG (10 mM), under the condition that colony learn more formation (about 1000 CFU per plate) was observed in the LB agar plate containing IAA (25 μg mL−1). This result suggested that the Trp-mediated inhibition of the target gene expression was sufficient for evaluation of the colony-forming capacity as a phenotype. When the strain targeting DnaB was examined, colonies were detected in the LB agar without any supplement, suggesting that these strains do not require DnaB at the higher expression level induced by IAA for colony formation. By contrast, the number of colonies was not altered by inducing the proteolytic system alone in the strains targeting DnaB, although the size of colonies was very small (data not shown). In strains in which the tnaA gene was not replaced with the trpR gene, the inhibition of colony formation was not observed in the LB agar plates containing Trp, suggesting that the tryptophanase activity of endogenous TnaA interferes with the Trp-mediated inhibition of Ptrp in this system (data not shown).

01]. Finally, we observed that more hepatotoxic events occurred during the first year of NNRTI therapy compared with the entire period after 1 year (6.6 vs. 2.8 events, respectively, per 100 person-years of treatment; P = 0.04). Long-term NNRTI use was not associated with a higher risk of clinically significant liver toxicity in patients who had been treated with NNRTI for at least 3 years. Following the introduction of highly active antiretroviral therapy ICG-001 datasheet (HAART), the life expectancy of HIV-infected patients has increased dramatically. In view of the facts that

HAART is a life-long therapy and a successful regimen is intended to be used for many years, the long-term side effects of these antiretroviral drugs are receiving increasing attention. The nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz (EFV) and nevirapine (NVP) are frequently used as components of current antiretroviral regimens. However, NNRTIs are known for their potential to cause hepatotoxicity, which can lead to morbidity and therapy switches. Different studies have reported a cumulative

incidence of severe hepatotoxicity Alpelisib varying from 1.4 to 15.6% in patients treated with NVP [1-5] and from 1.1 to 10% in patients treated with EFV [1-4]. However, the follow-up time in these studies was relatively short, up to 3 years. Data focusing on hepatotoxicity in long-term NNRTI use are scarce [6]. The aim Chlormezanone of this retrospective cohort analysis was to evaluate whether the incidence of hepatotoxicity increases with increasing duration of an NNRTI regimen. All HIV-infected patients under follow-up at our clinic until 1 November 2009, who had been receiving an NNRTI-containing HAART regimen for ≥ 3 years, were identified. Patients were included in the analysis if they had continuously used the same NNRTI for a minimum of three years and if at least one serum alanine transaminase (ALT) value per year was available throughout the treatment period. The control group consisted of patients who had exclusively received a protease inhibitor

(PI)-based regimen for at least 3 years and for whom ALT data were available. Demographic, pharmacological and laboratory data at the start of therapy were retrieved from the clinical database and patient records. Patients were considered to have a hepatitis B virus (HBV) infection when HBV DNA and/or the HBV surface antigen (HBsAg) was found at baseline. Hepatitis C virus (HCV) infection was defined as the detection of HCV RNA by polymerase chain reaction. Patients for whom baseline ALT was unknown and those with acute viral hepatitis during NNRTI treatment were excluded from the analysis. Hepatotoxicity was graded according to the modified toxicity scale of the AIDS Clinical Trials Group [1]. Serum ALT values were used rather than serum aspartate aminotransferase (AST) or cholestatic liver enzymes, as ALT is considered to be a more specific marker for liver damage [7].

Disrupting these cortico-collicular projections at any stage of life results in a pattern of outcomes similar to those found after dark-rearing; SC neurons respond to stimuli in both sensory modalities, VX-809 chemical structure but cannot integrate the information they provide. Thus, it

is possible that dark-rearing compromises the development of these descending tecto-petal connections and the essential influences they convey. However, the results of the present experiments, using cortical deactivation to assess the presence of cortico-collicular influences, demonstrate that dark-rearing does not prevent the association cortex from developing robust influences over SC multisensory responses. In fact, dark-rearing may increase their potency over that observed in normally-reared learn more animals. Nevertheless, their influences are still insufficient to support

SC multisensory integration. It appears that cross-modal experience shapes the cortical influence to selectively enhance responses to cross-modal stimulus combinations that are likely to be derived from the same event. In the absence of this experience, the cortex develops an indiscriminate excitatory influence over its multisensory SC target neurons. “
“Very few studies have investigated to what extent different subtypes of specific phobia share the same underlying functional neuroanatomy. This study aims to investigate the potential differences in the anatomy and dynamics of the blood oxygen level-dependent (BOLD) responses associated with spider and blood-injection-injury phobias. We used an event-related paradigm in 14 untreated spider phobics, 15 untreated blood-injection-injury phobics and 17 controls. Phobic images successfully induced distress only in phobic participants. Both phobic groups showed a similar pattern of heart rate increase following the presentation of phobic stimuli, this being different from controls. The presentation of phobic check details images induced activity within the same brain network in all

participants, although the intensity of brain responses was significantly higher in phobics. Only blood-injection-injury phobics showed greater activity in the ventral prefrontal cortex compared with controls. This phobia group also presented a lower activity peak in the left amygdala compared with spider phobics. Importantly, looking at the dynamics of BOLD responses, both phobia groups showed a quicker time-to-peak in the right amygdala than controls, but only spider phobics also differed from controls in this parameter within the left amygdala. Considering these and previous findings, both phobia subtypes show very similar responses regarding their immediate reaction to phobia-related images, but critical differences in their sustained responses to these stimuli.